Hippocampal Neuronal Atrophy and Cognitive Function in Delayed Poststroke and Aging-Related Dementias

Centre for Brain Ageing and Vitality, Institute for Ageing and Health, Newcastle University, Campus for Ageing & Vitality, Newcastle upon Tyne, UK.
Stroke (Impact Factor: 5.72). 12/2011; 43(3):808-14. DOI: 10.1161/STROKEAHA.111.636498
Source: PubMed


We have previously shown delayed poststroke dementia in elderly (≥75 years old) stroke survivors is associated with medial temporal lobe atrophy; however, the basis of the structural and functional changes is unknown.
Using 3-dimensional stereological methods, we quantified hippocampal pyramidal neuronal volumes and densities in a total of 95 postmortem samples from demented and nondemented poststroke survivors within our prospective Cognitive Function after Stroke study and subjects pathologically diagnosed with vascular dementia, Alzheimer disease, and mixed Alzheimer disease and vascular dementia syndrome.
Hippocampal CA1 but not CA2 subfield neuron density was affected in poststroke, Alzheimer disease, vascular dementia, and mixed dementia groups relative to control subjects (P<0.05). Neuronal volume was reduced in the poststroke dementia relative to poststroke nondemented group in both CA1 and CA2, although there were no apparent differences in neuronal density. Poststroke nondemented neuronal volumes were similar to control subjects but greater than in all dementias (P<0.05). Neuronal volumes positively correlated with global cognitive function and memory function in both CA1 and CA2 in poststroke subjects (P<0.01). Degrees of neuronal atrophy and loss were similar in the poststroke dementia and vascular dementia groups. However, in the entorhinal cortex layer V, neuronal volumes were only impaired in the mixed and Alzheimer disease groups (P<0.05).
Our results suggest hippocampal neuronal atrophy is an important substrate for dementia in both cerebrovascular and neurodegenerative disease.

Download full-text


Available from: Vincent Deramecourt, May 29, 2015
19 Reads
    • "Indeed, neuroimaging studies in other disorders are sparse and seem to indicate that CA1 (± subiculum) is also the subfield of strongest atrophy in dementia with Lewy body (Sabattoli et al., 2008; Chow et al., 2012), and various subtypes of frontotemporal lobar degeneration (Lindberg et al., 2012; La Joie et al., 2013). Similarly, neuropathological studies have reported a strong CA1 neuronal loss in patients with vascular dementia (Kril et al., 2002; Gemmell et al., 2012). From a more practical point of view, the clinical feasibility of high-resolution hippocampus-centric MRI acquisitions is still uncertain because these scans are particularly prone to motion artifacts (for discussion, see Mueller and Weiner, 2009; La Joie et al., 2013). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Hippocampal atrophy, as evidenced using magnetic resonance imaging (MRI), is one of the most validated, easily accessible and widely used biomarkers of Alzheimer's disease (AD). However, its imperfect sensitivity and specificity have highlighted the need to improve the analysis of MRI data. Based on neuropathological data showing a differential vulnerability of hippocampal subfields to AD processes, neuroimaging researchers have tried to capture corresponding morphological changes within the hippocampus. The present review provides an overview of the methodological developments that allow the assessment of hippocampal subfield morphology in vivo, and summarizes the results of studies looking at the effects of AD and normal aging on these structures. Most studies highlighted a focal atrophy of the CA1 subfield in the early (predementia or even preclinical) stages of AD, before atrophy becomes more widespread at the dementia stage, consistent with the pathological literature. Preliminary studies have indicated that looking at this focal atrophy pattern rather than standard whole hippocampus volumetry improves diagnostic accuracy at the Mild Cognitive Impairment (MCI) stage. However, controversies remain regarding changes in hippocampal subfield structure in normal aging and regarding correlations between specific subfield volume and memory abilities, very likely because of the strong methodological variability between studies. Overall, hippocampal subfield analysis has proven to be a promising technique in the study of AD. However, harmonization of segmentation protocols and studies on larger samples are needed to enable accurate comparisons between studies and to confirm the clinical utility of these techniques. Copyright © 2015. Published by Elsevier Ltd.
    Neuroscience 08/2015; 309. DOI:10.1016/j.neuroscience.2015.08.033 · 3.36 Impact Factor
  • Source
    • "For this study, we assessed samples of both gray and white matter from the temporal lobe (Brodmann area 21). We focused on the temporal lobe because medial temporal lobe atrophy is a common finding in dementia and our recent study suggested a vascular basis for neurodegeneration (Gemmell et al., 2012). The temporal lobe is also relatively free of large infarcts (Kalaria et al., 2004). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Despite its importance as the leading cause of vascular dementia, the primary pathogenic mechanisms in subcortical ischemic vascular dementia (SIVD) have remained elusive. Because of the lack of approved therapeutic agents for SIVD, there is a pressing need to identify novel therapeutic targets. Comparative lipidomic analyses of SIVD and mixed dementia (i.e., SIVD and Alzheimer's disease, MixD) may also confer new insights pertaining to the possible interaction between neurodegenerative and vascular mechanisms in the pathogenesis of dementia. Liquid chromatography coupled to mass spectrometry was used to comprehensively analyze the lipidomes of white and gray matter from the temporal cortex of nondemented controls, SIVD, and MixD subjects. Detailed molecular profiles highlighted the pathologic relevance of gray matter sphingolipid fatty acyl chain heterogeneity in dementia. In addition, the levels of sulfatides and lysobisphosphatidic acids were progressively increased in the temporal cortex gray matter from control to SIVD to MixD. White matter phospholipid profiles indicated possible adaptive mechanisms (i.e., increased unsaturation) to chronic ischemia in SIVD and elevated membrane degradation in MixD.
    Neurobiology of aging 03/2014; 35(10). DOI:10.1016/j.neurobiolaging.2014.02.025 · 5.01 Impact Factor
  • Source
    • "While it may reflect methodological issues related to biomarker measurements (Jack et al., 2013), it is possible that CA1 atrophy in Aβnegative patients reflect non-AD pathophysiological processes. This would be consistent with the finding of CA1 atrophy in other disorders (Gemmell et al., 2012; Jack et al., 2002; Zarow et al., 2012) and the idea that aMCI in Aβ-negative patients is unlikely due to AD etiology (Albert et al., 2011). Alternatively, recent findings suggest that neuronal injury biomarkers known to be closely related to tau pathology such as hippocampal atrophy (see above), may occur independently and possibly prior to Aβ in the course of AD (Chételat, 2013; Knopman et al., 2013). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Hippocampal atrophy is a well-known feature of Alzheimer's disease (AD), but sensitivity and specificity of hippocampal volumetry are limited. Neuropathological studies have shown that hippocampal subfields are differentially vulnerable to AD; hippocampal subfield volumetry may thus prove to be more accurate than global hippocampal volumetry to detect AD. CA1, subiculum and other subfields were manually delineated from 40 healthy controls, 18 AD, 17 amnestic Mild Cognitive Impairment (aMCI), and 8 semantic dementia (SD) patients using a previously developed high resolution MRI procedure. Non-parametric group comparisons and receiver operating characteristic (ROC) analyses were conducted. Complementary analyses were conducted to evaluate differences of hemispheric asymmetry and anterior-predominance between AD and SD patients and to distinguish aMCI patients with or without β-amyloid deposition as assessed by Florbetapir-TEP. Global hippocampi were atrophied in all three patient groups and volume decreases were maximal in the CA1 subfield (22% loss in aMCI, 27% in both AD and SD; all p < 0.001). In aMCI, CA1 volumetry was more accurate than global hippocampal measurement to distinguish patients from controls (areas under the ROC curve = 0.88 and 0.76, respectively; p = 0.05) and preliminary analyses suggest that it was independent from the presence of β-amyloid deposition. In patients with SD, whereas the degree of CA1 and subiculum atrophy was similar to that found in AD patients, hemispheric and anterior-posterior asymmetry were significantly more marked than in AD with greater involvement of the left and anterior hippocampal subfields. The findings suggest that CA1 measurement is more sensitive than global hippocampal volumetry to detect structural changes at the pre-dementia stage, although the predominance of CA1 atrophy does not appear to be specific to AD pathophysiological processes.
    Clinical neuroimaging 08/2013; 3:155-62. DOI:10.1016/j.nicl.2013.08.007 · 2.53 Impact Factor
Show more